Association between chemotherapy-induced myelosuppression and curative efficacy of 2-cycle chemotherapy in small cell lung cancer.

BACKGROUND: The association of chemotherapy-induced myelosuppression with tumor response and overall survival remained controversial. The study was conducted to investigate the association between them in small cell lung cancer (SCLC). METHODS: 204 eligible patients with SCLC were respectively included and categorized into three groups (no, mild, and severe myelosuppression) based on myelosuppression degree after the first chemotherapy. Curative efficacy of 2-cycle chemotherapy was evaluated by the objective response rate (ORR) and disease control rate (DCR). Univariate and multivariate logistic regression analyses were conducted to investigate their association. Receiver operator characteristic (ROC) curves, net reclassification index (NRI), and integrated discrimination improvement (IDI) were used to assess the predictive ability of myelosuppression. RESULTS: In the fully-adjusted model, mild (OR, 4.61; 95% CI, 1.35 to 18.27; P = 0.020) and severe (OR, 7.22; 95% CI, 1.30 to 72.44; P = 0.046) myelosuppression were positively associated with DCR. However, only mild myelosuppression was significantly associated with ORR (OR, 2.78; 95% CI, 1.30 to 6.14; P = 0.010). Although we observed evidence of increased ORR in severe myelosuppression, the difference was not statistically significant. Furthermore, based on the results of the ROC curve, NRI and IDI, chemotherapy-induced myelosuppression cannot be used as a accurate and independent predictor for curative efficacy, but it can improve overall prediction accuracy. CONCLUSION: Chemotherapy-induced myelosuppression was significantly associated with curative efficacy of 2-cycle chemotherapy in SCLC, which could help predict treatment efficacy and guide chemotherapy dosage.

Frailty in asthma-COPD overlap: a cross-sectional study of association and risk factors in the NHANES database.

BACKGROUND: Asthma-chronic obstructive pulmonary disease (COPD) overlap (ACO) is a condition characterised by the simultaneous presence of features of both asthma and COPD. The study aims to investigate the association between ACO and frailty among middle-aged and elderly populations, and identify the risk factors for frailty in individuals with ACO. METHODS: We conducted a cross-sectional study with 34 403 eligible participants (aged ≥40 years) from the National Health and Nutrition Examination Survey 1999-2018 cycles. Participants were stratified into four groups: ACO, asthma, COPD and non-asthma/COPD. Frailty assessment was based on frailty index, generating frail and non-frail group. Univariate and multivariate survey-weighted logistic regression analysis were used to determine the association between ACO and frailty, and to identify the risk factors for frailty in ACO. RESULTS: The frailty prevalence in participants with ACO was 60.2%, significantly higher than that in those with asthma (32.3%) and COPD (40.6%). In the unadjusted model, participants with ACO exhibited six-fold higher odds of frailty (OR 6.30, 95% CI 5.29 to 7.49), which was significantly greater than those with COPD (OR 2.84, 95% CI 2.46 to 3.28) and asthma (OR 1.99, 95% CI 1.80 to 2.18), using the non-asthma/COPD group as a reference. After adjusting for all confounders, participants with ACO had over four times higher odds of frailty (OR 4.48, 95% CI 3.53 to 5.71), still higher than those with asthma and COPD. The findings remained robust in sensitivity and subgroup analyses. Furthermore, hypertension, cancer, cardiovascular disease, chronic kidney disease and cognitive disorders were identified as risk factors for frailty among ACO participants, while higher income and education levels were protective factors. CONCLUSION: Patients (aged ≥40 years) with ACO were at a higher risk of frailty, regardless of age or sex, compared with those with asthma or COPD alone. Greater attention should be paid to patients with ACO, regardless of their age.

Is routine drainage necessary after thyroid surgery? A randomized controlled trial study.

Objective: To evaluate whether no drainage has an advantage over routine drainage in patients with thyroid carcinoma after unilateral thyroid lobectomy and central neck dissection. Methods: A total of 104 patients with thyroid cancer who underwent unilateral thyroid lobectomy and central lymph node dissection were randomly assigned into no drainage tube (n=52) and routine drainage tube (n=52) placement groups. General information of each patient was recorded, including the postoperative drainage volume/residual cavity fluid volume, postoperative complications, incision area comfort, and other data, and the thyroid cancer-specific quality of life questionnaire (THYCA-QoL) and patient and observer scar assessment scale (POSAS) were evaluated after surgery. At the 3-6 month follow-up exam, the differences between the two groups were compared based on univariate analysis. Results: Significant differences were not observed in the general and pathological information (including sex, age, body weight, body mass index (BMI), incision length, specimen volume, Hashimoto's thyroiditis, and number of lymph nodes dissected), operation time, and postoperative complications (postoperative bleeding, incision infection, lymphatic leakage, and temporary hypoparathyroidism) between the two groups. The patients in the non-drainage group had a shorter hospital stay (2.11 ± 0.33 d) than the patients in the drainage group (3.38 ± 0.90 d) (P<0.001). The amount of cervical effusion in patients in the non-drainage group (postoperative 24h: 2.20 ± 1.24 ml/48 h: 1.53 ± 1.07 ml) was significantly less than that in the drainage group (postoperative 24 hours: 22.58 ± 5.81 ml/48 h: 36.15 ± 7.61 ml) (all P<0.001). The proportion of incision exudation and incision numbness in the non-drainage group was lower than that in the drainage group (all P<0.05), and the pain score (VAS) and neck foreign body sensation score (FBST) decreased significantly (P<0.05). During the 3- and 6-month follow-up exams, significant differences were not observed between the THYCA-QoL and drainage groups and the non-drainage group, although the scarring and POSAS values were lower than those in the drainage group. In addition, the length of stay and cost of hospitalization in the non-drainage group were lower than those in the drainage group (P<0.05). Conclusion: Routine drainage tube insertion is not needed in patients with unilateral thyroid lobectomy and central neck dissection.

Association of weight range with telomere length: A retrospective cohort study.

Objective: Previous research has shown a significant association between weight and telomere length, but did not take into consideration weight range. The study was to investigate the association of weight range with telomere length. Methods: Data of 2918 eligible participants aged 25-84 years from the National Health and Nutrition Examination Survey (NHANES) 1999-2000 cycle were analyzed. Information about demographic variables, lifestyle factors, anthropometric variables, and medical comorbidities were included. Univariate and multivariate linear regression model with adjustments for potential confounders were employed to determine the association between weight range and telomere length. A non-parametrically restricted cubic spline model was used to illustrate the possible non-linear relationship. Results: In univariate linear regression, BMImax, BMI range, and weight range all revealed significant negative associations with telomere length. However, annual rate of BMI/weight range showed a significant positive associations with telomere length. There was no significant association between telomere length and BMImin. After adjusting for potential confounders, the inverse associations persisted in BMImax (ß=-0.003, P<0.001), BMI range (ß=-0.002, P=0.003), and weight range (ß=-0.001, P=0.001). Furthermore, annual rate of BMI range (ß=-0.026, P=0.009) and weight range (ß=-0.010, P=0.007) presented negative associations with telomere length, after adjusting for covariates in Model 2-4. The association between BMImin (ß =-0.002, P=0.237) and telomere length still could not reach statistical significance in multivariate linear regression model. The results of restricted cubic spline analysis showed that BMImax (P for nonlinear =0.026), BMI range (P for nonlinear =0.022), weight range (P for nonlinear =0.035), annual rate of BMI range (P for nonlinear =0.030), and annual rate of weight range (P for nonlinear =0.027) all had nonlinear inverse associations with telomere length. Conclusions: The study suggests that weight range is inversely associated with telomere length in U.S. adults. Larger weight fluctuation may accelerate telomere shortening and aging.

Potential role of LPAR5 gene in prognosis and immunity of thyroid papillary carcinoma and pan-cancer.

Papillary carcinomas account for the largest proportion of thyroid cancers, with papillary thyroid carcinoma (PTC) being prone to early lymph node metastasis. Some studies have confirmed that LPAR5 can promote the progression of PTC, but immune-related analyses of LPAR5 and PTC have not been widely discussed. This study aimed to determine the role of LPAR5 in PTC prognosis and immunity. We will further explore the role of LPAR5 in 33 different tumor types. Regarding PTC, we analyzed the effect of LPAR5 expression on overall survival (OS). Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed. Immune-related analyses of immune checkpoints (ICPs) and immune cell infiltration were also performed. For pan-cancer, R packages were used to analyze prognosis, tumor mutational burden (TMB), microsatellite instability (MSI), and immune cell infiltration. Analysis of tumor microenvironment (TME) and ICPs was performed using Sangerbox ( http://vip.sangerbox.com/home.html ). The TISIDB database ( http://cis.hku.hk/TISIDB/index.php ) was used to identify immune and molecular subtypes. LPAR5 expression is associated with PTC prognosis and immunity as well as various human tumors. LPAR5 may be a potential biomarker for multiple malignancies and may provide a new target for cancer immunotherapy.

Advances in the treatment of secondary and tertiary hyperparathyroidism.

Secondary hyperparathyroidism (SHPT) and tertiary hyperparathyroidism (THPT) are common and complicated clinical endocrine diseases. The parathyroid glands maintain endocrine homeostasis by secreting parathyroid hormone to regulate blood calcium levels. However, structural alterations to multiple organs and systems occur throughout the body due to hyperactivity disorder in SHPT and THPT. This not only decreases the patients' quality of life, but also affects mortality. Since current treatments for these diseases remains unclear, we aimed to develop a comprehensive review of advances in the treatment of SHPT and THPT according to the latest relevant researches.

Inflammation and histone modification in chronic pain.

Increasing evidence suggests that epigenetic mechanisms have great potential in the field of pain. The changes and roles of epigenetics of the spinal cord and dorsal root ganglia in the chronic pain process may provide broad insights for future pain management. Pro-inflammatory cytokines and chemokines released by microglia and astrocytes, as well as blood-derived macrophages, play critical roles in inducing and maintaining chronic pain, while histone modifications may play an important role in inflammatory metabolism. This review provides an overview of neuroinflammation and chronic pain, and we systematically discuss the regulation of neuroinflammation and histone modifications in the context of chronic pain. Specifically, we analyzed the role of epigenetics in alleviating or exacerbating chronic pain by modulating microglia, astrocytes, and the proinflammatory mediators they release. This review aimed to contribute to the discovery of new therapeutic targets for chronic pain.

Development of a Double-Antibody Sandwich ELISA for Rapid Detection of the MCP Antigen Concentration in Inactivated ISKNV Vaccines.

Infectious spleen and kidney necrosis virus (ISKNV) resulted in severe systemic diseases with high morbidity and mortality in Siniperca chuatsi. Vaccination is the primary method for effective prevention and control of these diseases. The development of inactivated ISKNV vaccines made some progress, but the technique of quality evaluation is scarce. Herein, a measurement of the MCP (major capsid protein) antigen concentration for the inactivated ISKNV vaccine was developed by double-antibody sandwich ELISA. Firstly, mouse monoclonal antibodies against ISKNV particles and MCP were generated. Then, a double-antibody sandwich ELISA was developed using the monoclonal antibody 1C8 1B9 as the capture antibody and Biotin-3B12 6B3 as the detection antibody. A standard curve was generated using the MCP concentration versus OD value with the linear range of concentration of 4.69~300 ng/mL. The assay sensitivity was 0.9 ng/mL. The antigen content of three batches of inactivated ISKNV vaccines was quantitatively detected using the double-antibody sandwich ELISA. The results showed that MCP antigen contents of inactivated ISKNV vaccines were positively correlated with the viral titers. The newly established double-antibody sandwich ELISA provided a useful tool for the detection of antigen quality for ISKNV inactivated vaccines.

Myocardial involvement in idiopathic inflammatory myopathies: a multi-center cross-sectional study in the CRDC-MYO Registry.

OBJECTIVES: This study aimed to investigate the associated factors of myocardial involvements (MIs) in patients with idiopathic inflammatory myopathies (IIMs). METHODS: In this multi-center cross-sectional study, 1946 patients with IIMs were enrolled from Chinese Rheumatism Data Center-Myositis Registry (CRDC-MYO). A total of 108 (5.5%) patients were identified with MIs, including congestive heart failure (n = 67, 62.0%), and severe arrhythmias (n = 61, 56.5%). The other 1838 IIM patients without IMs were set as the control group. Clinical features were collected including age, gender, comorbidities, clinical symptoms, clinical signs of both IIMs and MIs, lab findings including myositis-specific antibodies (MSAs) and myositis-associated antibodies (MAAs), echocardiogram, and radiological exams. Multivariate logistic analysis was used to explore independent associated factors of MIs in patients with IIMs. RESULTS: Several independent associated factors were identified in multi-variate logistic regression, including positivity for anti-mitochondrial antibody-subtype 2 (AMA-M2) (OR 5.194, 95% CI 2.509-10.753, P < 0.001), elevation of creatine kinase (CK) (OR 2.611, 95% CI 1.312-5.198, P = 0.006), elevation of C-reactive protein (CRP) (OR 2.150, 95% CI 1.211-3.818, P = 0.001), and pulmonary hypertension (OR 4.165, 95% CI 1.765-9.882, P = 0.009). AMA-M2 and pulmonary hypertension were the most consistent associated factors in the polymyositis subgroup and the dermatomyositis/clinically amyopathic dermatomyositis subgroup. CONCLUSIONS: MIs are rare but serious complication of IIMs could lead to congestive heart failure and severe arrhythmias. IIM patients with AMA-M2 positivity, elevation of CK and CRP, and pulmonary hypertension are more likely to develop MI complications. Key Points • This study investigated the independent associated factors for clinically significant myocardial involvements among idiopathic inflammatory myopathies in a large-scale, nation-wide multi-center cross-sectional study.

Identification of intron in ORF003 gene and its application for inactivation test of ISKNV.

The virus inactivation test is a critical skill in inactivated vaccine production. Active viruses produced viral mRNA in susceptible cells or the host can be used to infer whether a DNA virus is replicating by RT-PCR. But it is generally difficult to avoid genomic DNA contamination in the samples. However, the use of primers spanning an intron is an effective alternative for virus inactivation test. Therein, a nested RT-PCR was developed to detect active ISKNV in the inactivated vaccine. At first, the transcriptome analysis of CPB cell infected with ISKNV revealed several gaps in some viral transcripts compared to ISKNV genome. One intron in ORF003L with 80 bp (designated IN-3) was confirmed by PCR and sequencing analysis. Then, two primer sets (primer A and primer B) spanning the IN-3 intron were designed to detect ISKNV transcription. The nested RT-PCR conditions were optimized with 0.4 µM primer A and 0.2 µM primer B, and 68 °C and 55 °C for annealing temperature, respectively. The sensitivity results indicated that the nested RT-PCR could detect one copy of live ISKNV propagating in CPB cells for seven days. The nested RT-PCR method was more sensitive and accurate than the method of blind passages in cells and fish challenge experiments. Together, above results indicate that this assay is a time-saving, labor-extensive and cost-effective for inactivation test of ISKNV in killed vaccine production.

Early short-term ivabradine treatment in new-onset acute systolic heart failure and sinus tachycardia patients with inflammatory rheumatic disease.

Acute heart failure (AHF) is a common complication of inflammatory rheumatic disease (IRD) and usually coexists with tachycardia. Ivabradine, a direct sinus node inhibitor, which was proven to have favorable effects in patients with chronic HF (CHF), has not been sufficiently evaluated in AHF patients regarding its efficacy and safety. The present study sought to explore the effectiveness of early short-term ivabradine treatment in new-onset AHF and concurrent sinus tachycardia in patients with IRD. A total of 12 consecutive patients with IRD, who had new-onset AHF and concurrent sinus tachycardia, were prescribed ivabradine and were retrospectively recruited. Standard medication therapy for AHF was also administered. The heart rate (HR), left ventricular ejection fraction (LVEF), biomarkers of HF and New York Heart Association (NYHA) classification score were compared prior to and after ivabradine treatment. After 48 h of treatment with ivabradine, the mean resting HR decreased from 118.0±13.8 to 83.3±7.3 bpm (P<0.001). Transthoracic echocardiography indicated a significant improvement in the LVEF on an average of 2 weeks after ivabradine prescription when compared with the baseline evaluation (51.2±8.4 vs. 38.0±9.0%; P<0.001). In addition, ivabradine treatment resulted in significantly decreased N-terminal proB-type natriuretic peptide (4,900±3,672 vs. 16,806±16,130 pg/ml; P=0.045) and improvement of the NYHA classification score (2.3±0.6 vs. 3.5±0.5; P<0.001) at 2 weeks when compared with the baseline. Overall, the results of the present study suggested that early use of ivabradine is safe in IRD patients with new-onset AHF and enhances the sinus rate reduction, which may improve heart function.

Efficacy of non-invasive ventilation and oxygen therapy on immunocompromised patients with acute hypoxaemic respiratory failure: protocol for a systematic review and meta-analysis of randomised controlled trials.

BACKGROUND: The number of immunocompromised patients has increased in recent years. Acute respiratory failure is a common complication leading to intensive care unit (ICU) admission and high mortality among such patients. The use of non-invasive ventilation (NIV) or oxygen therapy among these patients remains controversial, according to the inconsistent results of several randomised clinical trials (RCTs). This meta-analysis aims to evaluate whether NIV or oxygen therapy is the more appropriate initial oxygenation strategy for the immunocompromised patients with acute respiratory failure. METHOD: We will search all the RCTs that compared the efficacy of NIV and oxygen therapy on immunocompromised adult patients with acute hypoxaemic respiratory failure on the major databases (Cochrane Library, MEDLINE, EMBASE, Web of Science and others), conference proceedings and grey literature. Eligible RCTs will be included in accordance with the pre-specified eligibility criteria. The risk of bias will be assessed using the Cochrane Collaboration criteria and the quality of evidence will be assessed with the Grading of Recommendations Assessment, Development and Evaluation system. Data will be extracted with a standardised form and analysed using RevMan V.5.3 analyses software. Heterogeneity will be assessed using I2 statistic and the source of which will be investigated. Publication bias will be identified with the funnel plot. ETHICS AND DISSEMINATION: Ethical approval is not required since it is not carried out in humans. The systematic review will be published in peer-reviewed journals and disseminated extensively through conferences.

Noninvasive versus invasive mechanical ventilation for immunocompromised patients with acute respiratory failure: a systematic review and meta-analysis.

BACKGROUND: To determine the effects of noninvasive mechanical ventilation (NIV) compared with invasive mechanical ventilation (IMV) as the initial mechanical ventilation on clinical outcomes when used for treatment of acute respiratory failure (ARF) in immunocompromised patients. METHODS: We searched PubMed, EMBASE, the Cochrane Central Register of Controlled Trials (CENTRAL), the Chinese Biomedical Literature Database (CBM) and other databases. Subgroup analyses by disease severity and causes of immunodeficiency were also conducted. RESULTS: Thirteen observational studies with a total of 2552 patients were included. Compared to IMV, NIV was shown to significantly reduce in-hospital mortality (OR 0.43, 95 % CI 0.23 to 0.80, P value = 0.007) and 30-day mortality (OR 0.34, 95 % CI 0.20 to 0.61, P value < 0.0001) in overall analysis. Subgroup analysis showed NIV had great advantage over IMV for less severe, AIDS, BMT and hematological malignancies patients in reducing mortality and duration of ICU stay. CONCLUSIONS: The overall evidence we obtained shows NIV does more benefits or at least no harm to ARF patients with certain causes of immunodeficiency or who are less severe.

Pneumothorax as the initial manifestation of idiopathic hypereosinophilic syndrome.

We report a case of hypereosinophilic syndrome in a 47-year-old man who had acute pneumothorax as the initial presentation. Peripheral blood eosinophil count increased continuously over a period of 1 month and was associated with pulmonary changes and appearance of skin lesions on the right chest wall. Idiopathic hypereosinophilic syndrome was confirmed by bone marrow aspiration biopsy and skin lesion biopsy after exclusion of all possible secondary etiologies. The clinical status and chest radiographs showed marked improvement after treatment with corticosteroids.

[Surgical treatment of ascending aortic aneurysm by Bentall's procedure: report of 14 cases].

OBJECTIVE: To review our experience in surgical treatment of ascending aortic aneurysm (AAA) with aortic insufficiency in 14 cases of by Bentall's procedure. METHODS AND RESULTS: All the patients underwent replacement of the ascending aorta and aortic valve with composite valved vascular prosthesis and received direct implantation of the aortic graft of the coronary orifices (Bentall's procedure) with satisfactory results. Five patients had ascending aortic dissection and 4 had typical Marfan's syndrome. All the patients suffered severe aortic insufficiency while 2 had mitral insufficiency. Coronary orifices were implanted in situ in 13 cases while in 1 case, Cabrol's method was adopted. No death occurred during the surgery and in the subsequent follow-up, and all the patients had good recovery. CONCLUSION: Bentall's procedure can be effective in the treatment of AAA with aortic insufficiency.